Methods and Devices For Determining Lumen Occlusion

ABSTRACT

Embodiments of the present invention describe methods of determining the occlusion of body lumens and apparatuses for doing so. In one particular embodiment, the occlusion of the fallopian tubes by an intrafallopian contraceptive device may be confirmed by contrast enhanced ultrasonography (also known as stimulated acoustic emission hysterosalpingo-contrast sonography). In these embodiments a contrast agent containing microbubbles is used.

The present application is a continuation of U.S. patent applicationSer. No. 11/472,102 filed on Jun. 20, 2006, now U.S. Pat. No. 8,123,693,which claims the benefit of priority from U.S. Provisional ApplicationNo. 60/692,497, filed Jun. 20, 2005, both of which are incorporatedherein by reference in their entirety.

BACKGROUND

1. Field

The present invention relates to the field of hysterosalpingo-contrastsonography and in particular the field of enhanced emissionhysterosalpingo-contrast sonography.

2. Discussion of Related Art

Female contraception and/or sterilization may be affected bytranscervically introducing an object (e.g. a coil) into a fallopiantube to inhibit conception. Devices, systems and methods for such acontraceptive approach have been described in various patents and patentapplications assigned to the present assignee. For example, U.S. Pat.No. 6,526,979 and U.S. Pat. No. 6,634,361 describe devices that aretranscervically inserted into an ostium of a fallopian tube andmechanically anchored within the fallopian tube, both of these patentsare hereby incorporated by reference. The devices described in thesepatents and patent applications may promote a tissue in-growth aroundand within the inserted device, which may be referred to as an implantor an insert. One example of such devices is the device known as“Essure” from Conceptus, Inc. of San Carlos, Calif.. This tissuein-growth tends to provide long-term contraception and/or permanentsterilization by occlusion of the fallopian tubes without the need forsurgical procedures.

The intrafallopian contraceptive devices are non-surgically positionedwithin the fallopian tubes of a patient by a doctor within the doctor'soffice. The determination of the placement of the intrafallopiancontraceptive device within the fallopian tube after the procedure istypically done at a later point at a hospital by radiography. Theinability to confirm the placement of the device at the time ofplacement within the doctor's office creates difficulty for the patientand increases costs by requiring the patient to come in again foranother placement procedure of the intrafallopian contraceptive deviceif the placement was not done properly in the first place.

Several months after placement of the intrafallopian contraceptivedevice, the intrafallopian contraceptive devices within the fallopiantubes are visualized by a method such as radiography to determinewhether full occlusion of the fallopian tubes has occurred. This mustalso be performed in a hospital and may require a follow-up visit to adoctor, placing a burden on the patient and creating further expense.

Visualizing the intrafallopian contraceptive devices by ultrasoundperformed with saline may be difficult because saline looks the same asother fluids in the body. It therefore introduces a greater amount ofuncertainty in the determination of whether the devices have beenproperly positioned or whether the fallopian tubes or other type of bodylumen is occluded.

SUMMARY

Embodiments of the present invention describe methods of determining theocclusion of body lumens. In one particular embodiment, the occlusion ofthe fallopian tubes by an intrafallopian contraceptive device may beconfirmed by contrast enhanced ultrasonography (also known as stimulatedacoustic emission hysterosalpingo-contrast sonography). In theseembodiments a contrast agent containing microbubbles is used.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of the use of a balloon catheter to deliver anechogenic contrast agent containing microbubbles to a uterus and a pairof fallopian tubes.

FIG. 2 is an illustration of a dual-barreled syringe having a staticmixer and a pressure gauge for the delivery of an echogenic contrastagent containing microbubbles.

FIG. 3 is an illustration of a kit for the placement and/or confirmationof the placement of intrafallopian contraceptive devices into fallopiantubes using contrast enhanced ultrasonography.

FIG. 4 is an illustration of the placement of an intrafallopiancontraceptive device into a fallopian tube.

FIG. 5 is an illustration of a cross section of a uterus and a pair ofoccluded fallopian tubes containing intrafallopian contraceptivedevices.

FIG. 6 is an illustration of a kit for the determination of theocclusion of the fallopian tubes using contrast enhancedultrasonography.

DETAILED DESCRIPTION

In the following description numerous specific details are set forth inorder to provide a thorough understanding of the present invention. Oneof ordinary skill in the art will understand that these specific detailsare for illustrative purposes only and are not intended to limit thescope of the present invention. Additionally, in other instances,well-known processing techniques and equipment have not been set forthin particular detail in order to not unnecessarily obscure the presentinvention.

Embodiments of the present invention describe methods of determining theocclusion of body lumens. In one particular embodiment, the occlusion ofthe fallopian tubes by an intrafallopian contraceptive device may beconfirmed by contrast enhanced ultrasonography (also known as stimulatedacoustic emission hysterosalpingo-contrast sonography). In theseembodiments a contrast agent containing microbubbles is used.

Contrast enhanced ultrasonography may be used to determine the occlusionof body lumens such as the fallopian tubes or the vas deferens. Anechogenic contrast agent containing microbubbles is first administeredto a body lumen, and the occlusion of the body lumen is then determinedwith contrast enhanced ultrasonography. In one embodiment, contrastenhanced ultrasonography may be used to determine the occlusion of thefallopian tubes to determine whether intrafallopian contraceptivedevices may be placed in the fallopian tubes. In this embodiment, theuterus and the fallopian tubes are distended with an echogenic contrastagent. The echogenic contrast agent contains microbubbles that enhancethe sonographic imaging of the uterus and the fallopian tubes, hence thename ultrasonography. The microbubbles serve to enhance B-modeultrasound signals from the uterine cavity and fallopian tubes to enablebetter visualization of these structures. In other words, themicrobubbles show up as white on an ultrasonogram, which makes it easyto determine where they are and where they are not. In this embodiment,as illustrated in FIG. 1, the cervix 102 is cannulated with a ballooncatheter 104. The balloon 106 is expanded within and around the cervix102 to maintain the balloon catheter in position to deliver theechogenic contrast agent 108 and to seal the cervix 102 to preventleakage of the echogenic contrast agent. The echogenic contrast agentmay be formed at the point of use. In one embodiment the echogeniccontrast agent may be saline, glycine, or a similar solution that hasbeen carbonated or shaken at the point of use to introduce microbubbles.For example, a carbon dioxide cartridge may be used to introducemicrobubbles into saline. In an alternate embodiment, the echogeniccontrast agent 108 may be a concentrated pre-formed echogenic contrastagent containing microbubbles that is reconstituted with saline (or asimilar type of solution). The ratio of the concentrated echogeniccontrast agent relative to the saline (diluent) may be in theapproximate range of 1:10 and 10:1, and more particularly approximately1:6 and 1:2. In another embodiment, the echogenic contrast agent may beused alone without any dilution by a diluent such as saline. Theconcentration of microbubbles within the echogenic contrast agent thatis injected into the uterus and the fallopian tubes may be in theapproximate range of 1 microbubbles/cm³ and 10,000,000 microbubbles/cm³.The mean diameter of the microbubbles may be in the approximate range of0.5 micrometers (um) and 6.0 um, and more particularly in theapproximate range of 2.0 um and 4.5 um. In this embodiment, theconcentrated pre-formed echogenic contrast agent may he for example anyof the agents listed in Table 1 below:

Concentrated Stabilizing Contrast Agent Gas Shell Manufacturer EchovistAir None Schering AG (SHU 454) Albunex Air Albumin Mallinkrodt MedicalLevovist Air Palmitic Acid Schering AG (SHU 508 A) DefinityPerfluoropropane Phospholipids Bristol-Myers Squibb MRX 115Perfluoropropane Phospholipids Bristol-Myers Squibb DMP 115Perfluoropropane Phospholipids Bristol-Myers Squibb EchogenDodecafluoro- Surfactant Bristol-Myers (QW3600) pentane Squibb OptisonOctafluoropro- Albumin GE Healthcare/ (FSO 60) pane Amersham MedicalPESDA Perfluorobutane Albumin GE Healthcare/ Amersham Medical QuantisonAir Albumin GE Healthcare/ Amersham Medical QW7437 PerfluorocarbonSurfactant GE Healthcare/ Amersham Medical Imavist PerfluorohexaneSurfactant IMCOR (Imagent Pharmaceuticals APO150) Sonovue SulphurPhospholipids Bracco International (BR1) hexafluoride BV Infoson NycomedBR14 Perfluorobutane Phopholipids Sonavist Air Cyanoacrylate Schering AG(SHU 563 A) Sonazoid Perfluorocarbon Surfactant Schering AG (NC100100)

The echogenic contrast agent containing microbubbles may be administeredto the uterus and the fallopian tubes using a delivery system. Thedelivery system may be, for example, a syringe or a catheter system.

In one particular embodiment, the concentrated echogenic agentcontaining microbubbles may be reconstituted or mixed with the saline atthe point of use using a dual-barreled syringe such as the oneillustrated in FIG. 2. In this embodiment, the dual-barreled syringe 200has a first barrel 202 containing a concentrated echogenic contrastagent and a second barrel 204 containing saline. The dual-barreledsyringe has a plunger that plunges both the concentrated echogeniccontrast agent from the first barrel 202 and the saline from the secondbarrel 204 at approximately the same rate. In this particularembodiment, the concentrated echogenic contrast agent is mixed with thesaline by a static mixer 208 that may be an integral part of the syringe200 design or may be a separate piece that has been coupled to thesyringe 200. The mixed echogenic contrast agent has a viscosity close tothat of water. Therefore, the mixed echogenic contrast agent may easilyflow into the uterus and the fallopian tubes and also increases thecomfort of the patient.

The pressure that is required to push the echogenic contrast agent andsaline mixture out of the syringe may be measured by a pressure gauge210 coupled to the tip of the syringe 200. By monitoring the pressurerequired to press the mixed echogenic contrast agent out of thedual-barreled syringe 200 it is possible to determine whether the uterusand fallopian tubes have been fully distended. For example, if thepressure is increasing it is an indication that the uterus and thefallopian tubes are almost fully distended. If the pressure isdecreasing, it may be an indication that the tissue and/or vasculatureis absorbing the echogenic contrast agent fluid or microbubbles. Apressure decrease may also indicate that there is a “leak” in the systemdown a fallopian tube, through the cervix, or through a perforation inthe uterus or cervix. In yet another situation, a pressure decrease mayindicate that the uterus, which is a muscle, is stretching into a largerdistended shape. If the pressure measured by the pressure gauge 210remains constant, then it is an indication that the system is closed andthat there is no fluid flow. Once the pressure becomes constant then theinjection of the echogenic contrast agent containing microbubbles may bestopped. By watching for when the measured pressure becomes constant,the pressure gauge 210 makes it possible to determine the point at whichto stop the distention of the uterus and the fallopian tubes to improvepatient comfort. Additionally, monitoring the measured pressure of thepressure gauge 210 may also help prevent the excess usage of the mixedechogenic contrast agent to save on costs because it is possible todetermine the time to stop injecting the agent. The dual-barreledsyringe may also include a luer lock 212, or other type of lock, to sealand to store the contents of the first barrel 202 and the second barrel204.

The dual-barreled syringe 200 may be coupled to the balloon catheter 104to form a delivery system as illustrated in FIG. 1 to deliver the mixedechogenic contrast agent to the uterus 116 and the fallopian tubes 114.The distal end 110 of the balloon catheter 104 may be positioned nearthe ostium 112 of a fallopian tube 114 or positioned near the middle ofthe uterus 116. Once the uterus 116 and the fallopian tubes 114 havebeen distended with the echogenic contrast agent that includesmicrobubbles 108 the occlusion of the fallopian tubes 114 may bedetermined by contrast enhanced ultrasonography. Different ultrasoundprocedures may be used to perform contrast enhanced ultrasonographyincluding sagittal (abdominal) ultrasound, coronal (vaginal) ultrasound,and three-dimensional ultrasound. An ultrasonogram is viewed todetermine whether the fallopian tubes are patent. If the fallopian tubesare not occluded, then an intrafallopian contraceptive device placementprocedure may be performed.

The intrafallopian contraceptive device placement procedure may beperformed using the kit illustrated in FIG. 3. FIG. 3 illustrates a kit300 including an intrafallopian contraceptive device placement device302 that includes one or two intrafallopian contraceptive devices. Thekit also includes a syringe 304 containing an echogenic contrast agent.The syringe 304 may be a dual-barreled syringe containing a concentratedechogenic contrast agent that includes microbubbles 108 and saline andhaving a static mixer 208 and a pressure gauge 210, as described above.The kit 300 may further include instructions describing the procedurefor the placement of the intrafallopian contraceptive devices within thefallopian tubes 114 using contrast enhanced ultrasonography. The syringe304 may be used to administer the echogenic contrast agent that includesmicrobubbles 108 to a fallopian tube 114 as described above bydistending the fallopian tubes 114 and the uterus 116 with the echogeniccontrast agent that includes microbubbles 108. The echogenic contrastagent that includes microbubbles 108 may be delivered through a catheterfed through a hysteroscope 400 or through a balloon catheter 104. Theintrafallopian contraceptive device delivery catheter 310 that iscoupled to the handle 312 of the delivery device 302 is positionedwithin the fallopian tube 114 to deposit the intrafallopiancontraceptive device in the correct position within the fallopian tube.FIG. 4A illustrates an embodiment of the positioning and deposition ofthe intrafallopian contraceptive device within the fallopian tube 114.The delivery catheter 310 containing the intrafallopian contraceptivedevice 402 is positioned within the uterus 116 with a hysteroscope 400.The intrafallopian contraceptive device 402 may be formed of an outercoil 404 and an inner coil 406. In an embodiment, the intrafallopiancontraceptive device 402 is positioned to span the UTJ 408 of thefallopian tube 114 when released from the delivery catheter 310 byretracting the sheath 410 that holds the outer coil 404 in thewound-down position. When released, the outer coil 404 expands to fillthe diameter of the fallopian tube 114 and holds the intrafallopiancontraceptive device 402 in place within the fallopian tube 114. Theinner coil 406 may include fibers to promote tissue in-growth of thefallopian tube 114 into the outer coil 404 and into the inner coil 406.The positioning of the inner coil 406 well within the UTJ is thereforeimportant to promote tissue in-growth into the intrafallopiancontraceptive device 402. The verification of the proper placement ofthe intrafallopian contraceptive device 402 within the fallopian tube114 in the correct position using contrast enhanced ultrasonography maytherefore improve the accuracy of the positioning of the intrafallopiancontraceptive device within the UTJ. The position of each of theintrafallopian contraceptive devices after placement within each of thefallopian tubes provides immediate confirmation of the placement andallows for immediate correction of poor placement of the intrafallopiancontraceptive devices. The microbubbles within the echogenic contrastagent may cling to the intrafallopian contraceptive devices 402 toimprove the visibility of the devices on an ultrasonogram.

In an alternate embodiment, the uterus 116 and the fallopian tubes 114may be distended with the echogenic contrast media containingmicrobubbles after the placement of the intrafallopian contraceptivedevices 402 within the fallopian tubes 114 to verify the positioning ofthe devices within the fallopian tubes 114. Furthermore, the properpositioning of the intrafallopian contraceptive devices 402 transversingthe UTJ of the fallopian tubes 114 may be confirmed.

In another embodiment, the occlusion of the fallopian tubes 114 bytissue in-growth into the intrafallopian contraceptive devices 402 aftertheir placement (or by other approaches which cause occlusion of thefallopian tubes) may be verified by the use of contrast enhancedultrasonography. FIG. 5 illustrates intrafallopian contraceptive devices402 within the fallopian tubes 114 and transversing the UTJ. Theconfirmation of the occlusion of the fallopian tubes 114 may occuranytime after the placement of the intrafallopian contraceptive devices402 within the fallopian tubes 114. In one embodiment, the confirmationof the occlusion of the intrafallopian tubes 114 by the intrafallopiancontraceptive devices 402 may be performed approximately 3 months afterthe placement procedure for the intrafallopian contraceptive devices402. The contrast enhanced ultrasonography of the uterus 116 and thefallopian tubes 114 is performed to both confirm fallopian tubeocclusion and to evaluate the position of the intrafallopiancontraceptive devices 402 within the fallopian tubes 114. The use ofcontrast enhanced ultrasonography to place the intrafallopiancontraceptive devices 402 may increase the likelihood that the devicesare in the correct positions, but there is the possibility that thedevices may have moved over time. To perform contrast enhancedultrasonography the uterus 116 and the fallopian tubes 114 are firstdistended with an echogenic contrast agent containing microbubbles 108as described above. In one embodiment, a first ultrasonogram obtained bycontrast enhanced ultrasonography may be performed after a small amountof the echogenic contrast agent containing microbubbles 108 is instilledinto the uterus 116. This image should demonstrate evidence of anadequate seal of the cervix 102 and the beginning of pacification of theuterus 116. In this ultrasonogram the echogenic contrast agentcontaining microbubbles 108 is not likely to have reached the uterinecornua near the ostium 502 of the fallopian tubes 114 as illustrated inFIG. 5. Additionally, if the uterine cavity 116 is not seen clearly atthis point then it may be an indication that the position of the patientneeds to be adjusted for a better image. A second ultrasonogram may thenbe taken to provide an image of the uterus 116 when it is nearly full ofthe echogenic contrast media containing microbubbles 108. At this point,the cornua may not yet have been adequately distended. The proximalportions of the intrafallopian contraceptive devices 204 that trail intothe uterus 116 may not yet be obscured by the advancing contrast. Athird ultrasonogram may be obtained once the entire uterus 116 has beenfilled and distended. If a syringe that includes a pressure gauge isused to deliver the echogenic contrast media containing microbubbles108, then the distention of the uterus 116 may be estimated based on themeasurements of the pressure gauge. Once the uterus 116 is distended,the distal ends of the intrafallopian contraceptive devices 204 may beobscured by the echogenic contrast agent containing microbubbles 108.The microbubbles may stick to the distal ends of the intrafallopiancontraceptive devices 204 to increase their visibility by enhancedcontrast ultrasonography. If the fallopian tubes 114 have been occludedby tissue in-growth into the intrafallopian contraceptive devices 402,then the echogenic contrast agent containing microbubbles 108 will nothave permeated into the fallopian tubes 114, providing an ultrasonogramthat indicates the occlusion of the fallopian tubes 114. The positionsof the intrafallopian contraceptive devices 402 may be determined by thelength of the distal end of the intrafallopian contraceptive devices 402that extend beyond the fallopian tubes 114 into the uterus 116.

An embodiment of a kit 600 for the determination of the occlusion of thefallopian tubes is illustrated in FIG. 6. The kit 600 may contain a dualbarreled syringe 304 containing a concentrated echogenic contrast mediaincluding microbubbles 108 within a first barrel 202 and saline within asecond barrel 204. The dual barreled syringe may also include a staticmixer 208 and a pressure gauge 210. The kit also contains instructionsfor use of the echogenic contrast agent containing microbubbles 108 tovisualize and intrafallopian contraceptive device 402 within a fallopiantube 114 at a time after initial placement of the intrafallopiancontraceptive device 402 to determine occlusion of the fallopian tube bycontrast enhanced ultrasonography. The instructions 602 may furtherinclude directions to continue use of a secondary contraceptive if oneor both of the fallopian tubes are not fully occluded by theintrafallopian contraceptive devices 402 or if one or both of theintrafallopian contraceptive devices 402 are not in the proper positiontransversing the UTJ of the fallopian tubes 114. The instructions 602may also include directions to discontinue use of a secondarycontraceptive if the fallopian tubes are fully occluded and theintrafallopian contraceptive devices 402 are in the appropriatepositions. A balloon catheter 104 may also be included in the kit todeliver the echogenic contrast agent including microbubbles 108.

It is to be appreciated that the disclosed specific embodiments are onlymeant to be illustrative of the present invention and one of ordinaryskill in the art will appreciate the ability to substitute features orto eliminate disclosed features. As such, the scope of the Applicant'sinvention is to be measured by the appended claims that follow.

1. A method of diagnosing fallopian tube patency comprising: inserting adistal end of a catheter within a uterus; coupling a dual-barreledsyringe to the catheter, wherein the dual-barreled syringe comprise afirst barrel containing a gas, a second barrel containing a liquid, aplunger, and a mixer; plunging the gas from the first barrel and theliquid from the second barrel into the mixer to create an echogeniccontrast agent including microbubbles in the liquid; plunging theechogenic contrast agent from the dual-barreled syringe, through thedistal end of the catheter and into the uterus and a pair of fallopiantubes adjacent the uterus; and evaluating the pair of fallopian tubesfor patency utilizing a contrast enhanced ultrasonography procedure. 2.The method of claim 1, wherein inserting the distal end of the catheterwithin the uterus comprises: inserting the distal end of a ballooncatheter into a uterus; and expanding a balloon on the balloon catheteragainst a cervix to maintain the balloon catheter in position and sealthe cervix.
 3. The method of claim 1, wherein inserting the distal endof the catheter within the uterus comprises feeding the catheter througha hysteroscope.
 4. The method of claim 1, wherein the liquid comprisessaline.
 5. The method of claim 1, wherein the liquid comprises glycine.6. The method of claim 1, wherein the dual-barreled syringe comprises aluer lock.
 7. The method of claim 1, wherein the contrast enhancedultrasonography procedure comprises sagittal ultrasound.
 8. The methodof claim 1, wherein the contrast enhanced ultrasonography procedurecomprises coronal ultrasound.
 9. The method of claim 1, wherein thecontrast enhanced ultrasonography procedure comprises three-dimensionalultrasound.
 10. The method of claim 1, wherein the contrast enhancedultrasonography procedure comprises viewing an ultrasonogram.
 11. Themethod of claim 1, wherein the mixer is a static mixer.